The 5-hydroxyfuran-2(5H)-one a useful platform molecule for development of new organocatalytic asymmetric one-pot reactions. – HFOrgCat

In the first part of our work, a variety of a,?-substituted chiral ?-lactone displaying a great structural diversity were obtained by a one-pot sequential addition of boronic acids followed by an intramolecular Passerini reaction. First, a step of enantioselective organocatalysis allowed the activation for the transfer of boronic acids on the hydroxyfuran-2(5H)-one; then the chiral adduct formed was engaged in an intramolecular Passerini reaction leading to the construction of the
lactone ring. In the second part of this work, our efforts focused then on the development of catalytic asymmetric alkylation reactions leading to the construction of ?-lactones bearing an allcarbon quaternary stereocenter. The used of organic enantioselective catalysis was envisioned for the creation of all-quaternary stereocenters. Asymmetric allylic reactions were carried out with a very good control of the selectivity of the reaction by the use of palladium and iridium complexes catalysts. Theses lactones bearing an [1,5]-diene scaffold were then engaged in a sigmatropic [3,3]
reaction opening a path for a new approach to functionalization of aromatic heterocycles.

We have proposed a new enantioselective catalytic activation method of 5-hydroxyfuran-2(5H)-one. Combining this method with a Passerini reaction give an effectively access to chiral lactones with high structural diversity. We also explored diverse catalytic asymmetric methods for the formation of all quaternary center. Specifically, the use of asymmetric allylic alkylation reactions on original substrates led us to study a new use of Cope reaction in organic synthesis.

The promising results obtained in the second part of the project will be published in due course.

Our first publication is a part of recent efforts engaged by our team and other in order to develop methodologies combining a organocatalytic activation step and a multicomponent reaction to generate structural diversity:
Bos, M., and Riguet, E.
Synthesis of Chiral ?-Lactones by One-Pot Sequential Enantioselective Organocatalytic Michael Addition of Boronic Acids and Diastereoselective Intramolecular Passerini Reaction. J. Org. Chem. 2014, 79, 10881-10889.
Highlighted in Org. Process Res. Dev. 2015, 19, 596-610

The 5-hydroxyfuran-2(5H)-one is a readily available renewable resource which can be obtained on large scale by the photooxygenation of furfural. The polyfunctional nature of this easily available starting material has led to its extensive use in organic synthesis. However the use of 5-hydroxyfuran-2(5H)-one in asymmetric synthesis is currently limited to a chiral auxiliary approach. We propose to develop a regioselective and enantioselective catalytic functionalization of this synthon by means of organocatalysis. Moreover transformations leading to valuable chiral molecules in a one-pot process will be studied. Mechanistic investigation of relevant transformations will be done by Electrospray Ionization Mass Spectrometry and Nuclear Magnetic Resonance spectrometry. The mechanistic data acquired will be used to improve catalyst development and optimization of reaction conditions.